tbuckley/cabot-search huggingface dataset:
Clinical Promise of Brain-Phenotype Modeling
Authors: Abigail S. Greene, R. Todd Constable
Journal: JAMA Psychiatry (2023)

Assessing the link between whole-brain activity and individual differences in cognition and behavior has the potential to offer insights into psychiatric disorder etiology and change the practice of psychiatry, from diagnostic clarification to intervention. To this end, recent application of predictive modeling to link brain activity to phenotype has generated significant excitement, but clinical applications have largely not been realized. This Review explores explanations for the as yet limited practical utility of brain-phenotype modeling and proposes a path forward to fulfill this clinical potential.Clinical applications of brain-phenotype models are proposed and will require coordinated collaboration across the relatively siloed fields of psychometrics and computational neuroscience. Such interdisciplinary work will maximize the reliability and validity of modeled phenotypic measures, ensuring that resulting brain-based models are interpretable and useful. The models, in turn, may shed additional light on the neurobiological systems into which each phenotypic measure taps, permitting further phenotype refinement.Together, these observations reflect an opportunity: bridging the divide between phenotypic measure development and validation and measure end use for brain-phenotype modeling holds the promise that each may inform the other, yielding more precise and useful brain-phenotype models. Such models can in turn be used to reveal the macroscale neural bases of a given phenotype, advancing basic neuroscientific understanding and identifying circuits that can be targeted (eg, via closed-loop neurofeedback or brain stimulation) to slow, reverse, or even prevent functional impairment.
Errors in Funding/Support
Journal: JAMA Cardiology (2023)

Amanda R. Jowell, BA; Amy A. Sarma, MD, MHS; Martha Gulati, MD, MS; Erin D. Michos, MD, MHS; Arthur J. Vaught, MD; Pradeep Natarajan, MD, MMSc; Camille E. Powe, MD; Michael C. Honigberg, MD, MPP
Full‐Scale Osteochondral Regeneration by Sole Graft of Tissue‐Engineered Hyaline Cartilage without Co‐Engraftment of Subchondral Bone Substitute
Authors: Xiaolei Nie, Jian Yang, Yon Jin Chuah, Wenzhen Zhu, Yvonne Peck, Pengfei He, Dong‐An Wang
Journal: Advanced Healthcare Materials (2023)

Adv. Healthcare Mater. 2020, 9, 1901304 https://doi.org/10.1002/adhm.201901304 In the published version of this article, there are two mistakes in Figure 3e. The right-hand column of images labeled "Col I 50-Day" should instead read "Col I 100-Day". Furthermore, the image for dLhCG in the right-hand column is also an incorrect image, caused by a mistake during figure collation. The correct Figure 3e is presented below. The authors confirm that this correction does not affect the overall results and conclusions of this work. The authors apologize for any inconvenience caused.
Unusual Source of Dysphagia in a Man in His Eighth Decade of Life
Authors: Shaina Ailawadi, Polsha Jules, Damian Valencia
Journal: JAMA Cardiology (2023)

This case report discusses a diagnosis of arteria lusoria in a man with a history of transthyretin cardiac amyloidosis who presented for evaluation of dysphagia and transcatheter aortic valve replacement.
An Alternative Mechanism of Subcellular Iron Uptake Deficiency in Cardiomyocytes
Authors: Yuanyuan Dai, Nadezda Ignatyeva, Hang Xu, Ruheen Wali, Karl Toischer, Sören Brandenburg, Christof Lenz, Julius Pronto, Funsho E. Fakuade, Samuel Sossalla, Elisabeth M. Zeisberg, Andreas Janshoff, Ingo Kutschka, Niels Voigt, Henning Urlaub, Torsten Bloch Rasmussen, Jens Mogensen, Stephan E. Lehnart, Gerd Hasenfuss, Antje Ebert
Journal: Circulation Research (2023)

Systemic defects in intestinal iron absorption, circulation, and retention cause iron deficiency in 50% of patients with heart failure. Defective subcellular iron uptake mechanisms that are independent of systemic absorption are incompletely understood. The main intracellular route for iron uptake in cardiomyocytes is clathrin-mediated endocytosis.We investigated subcellular iron uptake mechanisms in patient-derived and CRISPR/Cas-edited induced pluripotent stem cell-derived cardiomyocytes as well as patient-derived heart tissue. We used an integrated platform of DIA-MA (mass spectrometry data-independent acquisition)-based proteomics and signaling pathway interrogation. We employed a genetic induced pluripotent stem cell model of 2 inherited mutations (TnT [troponin T]-R141W and TPM1 [tropomyosin 1]-L185F) that lead to dilated cardiomyopathy (DCM), a frequent cause of heart failure, to study the underlying molecular dysfunctions of DCM mutations.We identified a druggable molecular pathomechanism of impaired subcellular iron deficiency that is independent of systemic iron metabolism. Clathrin-mediated endocytosis defects as well as impaired endosome distribution and cargo transfer were identified as a basis for subcellular iron deficiency in DCM-induced pluripotent stem cell-derived cardiomyocytes. The clathrin-mediated endocytosis defects were also confirmed in the hearts of patients with DCM with end-stage heart failure. Correction of the TPM1-L185F mutation in DCM patient-derived induced pluripotent stem cells, treatment with a peptide, Rho activator II, or iron supplementation rescued the molecular disease pathway and recovered contractility. Phenocopying the effects of the TPM1-L185F mutation into WT induced pluripotent stem cell-derived cardiomyocytes could be ameliorated by iron supplementation.Our findings suggest that impaired endocytosis and cargo transport resulting in subcellular iron deficiency could be a relevant pathomechanism for patients with DCM carrying inherited mutations. Insight into this molecular mechanism may contribute to the development of treatment strategies and risk management in heart failure.
Blood Donors' Preferences Toward Incentives for Donation in China
Authors: Yu Wang, Peicong Zhai, Shan Jiang, Chaofan Li, Shunping Li
Journal: JAMA Network Open (2023)

Importance Blood donation is critical for health care systems, but donor retention remains challenging. Understanding donors’ preferences can inform incentive design and improve retention rates. Objective To identify donor preferences for incentive attributes and their relative importance in promoting blood donation among Chinese donors in Shandong. Design, Setting, and Participants This survey study fielded a discrete choice experiment (DCE) with a dual response design among blood donors, analyzing the responses under forced and unforced choice settings. The study took place from January 1 to April 30, 2022, in 3 cities (Yantai, Jinan, and Heze) representing diverse socioeconomic strata in Shandong, China. Eligible participants were blood donors aged 18 to 60 years who had donated within the preceding 12 months. Participants were recruited using convenience sampling. Data were analyzed from May to June 2022. Exposure Respondents were presented with different blood donation incentive profiles, varying in health examination, blood recipient, honor recognition, travel time, and gift value. Main Outcome and Measure Respondent preferences for nonmonetary incentive attributes, attribute relative importance, willingness-to-discard values for attribute improvement, and estimated uptake of new incentive profiles. Results A total of 650 donors were invited, of which 477 were included for analysis. The respondents were predominately male (308 respondents [64.6%]), aged 18 to 34 years (291 respondents [61.0%]), and had undergraduate degrees or higher (286 respondents [59.9%]). Among the 477 valid respondents, the mean (SD) age was 31.9 (11.2) years. Respondents preferred comprehensive health examination, family members as recipients, central government recognition, 30-minute travel time, and a gift valued at 60 Renminbi (RMB). No significant differences were found between the model results of forced and unforced choice setting. Blood recipient was the most important attribute, followed by health examination and gifts, and then honor and travel time. Respondents were willing to discard RMB 32 (95% CI, 18-46) for an improved health examination and RMB 69 (95% CI, 47-92) for changing the recipient from themselves to family members. Scenario analysis estimated 80.3% (SE, 0.024) of donors would endorse the new incentive profile if the recipient was changed from themselves to family members. Conclusions and Relevance In this survey study, blood recipient, health examination, and gift value were perceived more important as nonmonetary incentives than travel time and honor recognition. Tailoring incentives according to these preferences may improve donor retention. Further research could help refine and optimize incentive schemes for blood donation promotion.
Survey: Millions of People in the US Forgo Medications to Reduce Costs
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association of Intraoperative Opioid Administration With Postoperative Pain and Opioid Use
Authors: Laura A. Santa Cruz Mercado, Ran Liu, Kishore M. Bharadwaj, Jasmine J. Johnson, Rodrigo Gutierrez, Proloy Das, Gustavo Balanza, Hao Deng, Akriti Pandit, Tom A. D. Stone, Teresa Macdonald, Caroline Horgan, Si Long (Jenny) Tou, Timothy T. Houle, Edward A. Bittner, Patrick L. Purdon
Journal: JAMA Surgery (2023)

Opioids administered to treat postsurgical pain are a major contributor to the opioid crisis, leading to chronic use in a considerable proportion of patients. Initiatives promoting opioid-free or opioid-sparing modalities of perioperative pain management have led to reduced opioid administration in the operating room, but this reduction could have unforeseen detrimental effects in terms of postoperative pain outcomes, as the relationship between intraoperative opioid usage and later opioid requirements is not well understood.To characterize the association between intraoperative opioid usage and postoperative pain and opioid requirements.This retrospective cohort study evaluated electronic health record data from a quaternary care academic medical center (Massachusetts General Hospital) for adult patients who underwent noncardiac surgery with general anesthesia from April 2016 to March 2020. Patients who underwent cesarean surgery, received regional anesthesia, received opioids other than fentanyl or hydromorphone, were admitted to the intensive care unit, or who died intraoperatively were excluded. Statistical models were fitted on the propensity weighted data set to characterize the effect of intraoperative opioid exposures on primary and secondary outcomes. Data were analyzed from December 2021 to October 2022.Intraoperative fentanyl and intraoperative hydromorphone average effect site concentration estimated using pharmacokinetic/pharmacodynamic models.The primary study outcomes were the maximal pain score during the postanesthesia care unit (PACU) stay and the cumulative opioid dose, quantified in morphine milligram equivalents (MME), administered during the PACU stay. Medium- and long-term outcomes associated with pain and opioid dependence were also evaluated.The study cohort included a total of 61 249 individuals undergoing surgery (mean [SD] age, 55.44 [17.08] years; 32 778 [53.5%] female). Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. In particular, increased fentanyl administration was associated with lower frequency of uncontrolled pain; a decrease in new chronic pain diagnoses reported at 3 months; fewer opioid prescriptions at 30, 90, and 180 days; and decreased new persistent opioid use, without significant increases in adverse effects.Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended outcome of increasing postoperative pain and opioid consumption. Conversely, improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery.
Prevalence of Disability and Use of Accommodation Among US Allopathic Medical School Students Before and During the COVID-19 Pandemic
Authors: Karina Pereira-Lima, Melissa A. Plegue, Ben Case, Bonnielin K. Swenor, Kurt Herzer, Rylee Betchkal, Lisa M. Meeks
Journal: JAMA Network Open (2023)

This survey study assesses self-disclosures of disability, disability types, and accommodation needs reported by US allopathic medical schools in 2021 vs 2015 and 2019.
Necrotizing enterocolitis, gut microbes, and sepsis
Authors: Johannes W. Duess, Maame E. Sampah, Carla M. Lopez, Koichi Tsuboi, Daniel J. Scheese, Chhinder P. Sodhi, David J. Hackam
Journal: Gut Microbes (2023)

Necrotizing enterocolitis (NEC) is a devastating disease in premature infants and the leading cause of death and disability from gastrointestinal disease in this vulnerable population. Although the pathophysiology of NEC remains incompletely understood, current thinking indicates that the disease develops in response to dietary and bacterial factors in the setting of a vulnerable host. As NEC progresses, intestinal perforation can result in serious infection with the development of overwhelming sepsis. In seeking to understand the mechanisms by which bacterial signaling on the intestinal epithelium can lead to NEC, we have shown that the gram-negative bacterial receptor toll-like receptor 4 is a critical regulator of NEC development, a finding that has been confirmed by many other groups. This review article provides recent findings on the interaction of microbial signaling, the immature immune system, intestinal ischemia, and systemic inflammation in the pathogenesis of NEC and the development of sepsis. We will also review promising therapeutic approaches that show efficacy in pre-clinical studies.
High-risk Prognostic Tumor Features of Squamous Cell Carcinomas in Organ Transplant Recipients Compared With the General Population
Authors: Nirmala Pandeya, Nicole Isbel, Scott Campbell, Daniel C. Chambers, Peter Hopkins, H. Peter Soyer, Zainab Jiyad, Elsemieke I. Plasmeijer, David C. Whiteman, Catherine M. Olsen, Adele C. Green
Journal: JAMA Dermatology (2023)

The extent to which major high-risk features of squamous cell carcinomas (SCCs) in organ transplant recipients (OTRs) differ from SCCs in the general population is not known.
Functional LTCC-β <sub>2</sub> AR Complex Needs Caveolin-3 and Is Disrupted in Heart Failure
Authors: Jose L. Sanchez-Alonso, Laura Fedele, Jaël S. Copier, Carla Lucarelli, Catherine Mansfield, Aleksandra Judina, Steven R. Houser, Thomas Brand, Julia Gorelik
Journal: Circulation Research (2023)

Beta-2 adrenergic receptors (β2ARs) but not beta-2 adrenergic receptors (β1ARs) form a functional complex with L-type Ca2+ channels (LTCCs) on the cardiomyocyte membrane. However, how microdomain localization in the plasma membrane affects the function of these complexes is unknown. We aim to study the coupling between LTCC and β adrenergic receptors in different cardiomyocyte microdomains, the distinct involvement of PKA and CAMKII (Ca2+/calmodulin-dependent protein kinase II) and explore how this functional complex is disrupted in heart failure.Global signaling between LTCCs and β adrenergic receptors was assessed with whole-cell current recordings and western blot analysis. Super-resolution scanning patch-clamp was used to explore the local coupling between single LTCCs and β1AR or β2AR in different membrane microdomains in control and failing cardiomyocytes.LTCC open probability (Po) showed an increase from 0.054±0.003 to 0.092±0.008 when β2AR was locally stimulated in the proximity of the channel (<350 nm) in the transverse tubule microdomain. In failing cardiomyocytes, from both rodents and humans, this transverse tubule coupling between LTCC and β2AR was lost. Interestingly, local stimulation of β1AR did not elicit any change in the Po of LTCCs, indicating a lack of proximal functional interaction between the two, but we confirmed a general activation of LTCC via β1AR. By using blockers of PKA and CaMKII and a Caveolin-3-knockout mouse model, we conclude that the β2AR-LTCC regulation requires the presence of caveolin-3 and the activation of the CaMKII pathway. By contrast, at a cellular "global" level PKA plays a major role downstream β1AR and results in an increase in LTCC current.Regulation of the LTCC activity by proximity coupling mechanisms occurs only via β2AR, but not β1AR. This may explain how β2ARs tune the response of LTCCs to adrenergic stimulation in healthy conditions. This coupling is lost in heart failure; restoring it could improve the adrenergic response of failing cardiomyocytes.
B-cell Receptor Pathway Mutations Are Infrequent in Patients with Chronic Lymphocytic Leukemia on Continuous Ibrutinib Therapy
Authors: Jennifer A. Woyach, Paolo Ghia, John C. Byrd, Inhye E. Ahn, Carol Moreno, Susan M. O'Brien, Daniel Jones, Leo W.K. Cheung, Elizabeth Chong, Kevin Kwei, James P. Dean, Danelle F. James, Adrian Wiestner
Journal: Clinical Cancer Research (2023)

Acquired mutations in Bruton's tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited.We evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 patients with previously untreated (n = 238) or relapsed/refractory (n = 150) CLL across five clinical trials.With median follow-up of 35 months (range, 0-72) without PD at last sampling, mutations in BTK (3%), PLCG2 (2%), or both genes (1%) were rare in previously untreated patients. With median follow-up of 35 months (range, 1-70) without PD at last sample, mutations in BTK (30%), PLCG2 (7%), or both genes (5%) were more common in patients with relapsed/refractory CLL. Median time to first detection of BTK C481S mutation was not reached in previously untreated patients and was >5 years in patients with relapsed/refractory CLL. Among patients evaluable at PD, previously untreated patients (n = 12) had lower rates than those with relapsed/refractory disease (n = 45) of BTK (25% vs. 49%) and PLCG2 mutations (8% vs. 13%). Time from first detection of BTK C481S mutation to PD was 11.3 months in 1 previously untreated patient and median 8.5 months (range, 0-35.7) among 23 patients with relapsed/refractory CLL.This systematic investigation describes development of mutations over time in patients without PD and informs the potential clinical opportunity to optimize ongoing benefits for such patients.
Use of Clinicians Who Focus on Nursing Home Care Among US Nursing Homes and Unplanned Rehospitalization
Authors: Seiyoun Kim, Kira L. Ryskina, Hye-Young Jung
Journal: JAMA Network Open (2023)

The number of physicians and advanced practitioners who focus their practice in nursing homes (NHs), often referred to as "SNFists" (ie, physicians, nurse practitioners, and physician assistants concentrating their practice in the nursing home or skilled nursing facility [SNF] setting) has increased dramatically. Little is known about the association of the NH medical care delivery models that use SNFists with the quality of postacute care.
Association of Mandatory Warning Signs for Cannabis Use During Pregnancy With Cannabis Use Beliefs and Behaviors
Authors: Sarah C. M. Roberts, Claudia Zaugg, M. Antonia Biggs
Journal: JAMA Network Open (2023)

Importance As states have legalized recreational cannabis use, some have enacted policies mandating point-of-sale warning signs with information on harms of using cannabis during pregnancy. While research has found such warning signs are associated with increased adverse birth outcomes, reasons why are unclear. Objective To examine whether exposure to cannabis warning signs is associated with cannabis-related beliefs, stigma, and use. Design, Setting, and Participants This cross-sectional study used data from a population-based online survey conducted from May to June 2022. Participants included pregnant and recently pregnant (within past 2 years) members of the national probability KnowledgePanel and nonprobability samples in all US states and Washington, the District of Columbia, where recreational cannabis is legal. Data were analyzed from July 2022 to April 2023. Exposure Living in 1 of 5 states with a warning signs policy. Main Outcomes and Measures Outcomes of interest were self-reported beliefs (linear) that cannabis use during pregnancy is not safe, should be punished, and is stigmatized and cannabis use during pregnancy (dichotomous). Regressions, accounting for survey weights and clustering by state, examined associations of warning signs with cannabis-related beliefs and use. Results A total of 2063 pregnant or recently pregnant people (mean [SD] weighted age, 32 [6] years) completed the survey, and 585 participants (weighted, 17%) reported using cannabis during their pregnancy. Among people who used cannabis during their pregnancy, living in a warning signs state was associated with beliefs that cannabis use during pregnancy was safe (β = −0.33 [95% CI, −0.60 to −0.07]) and that people who used cannabis during pregnancy should not be punished (β = −0.40 [95% CI, −0.73 to −0.07]). Among people who did not use cannabis before or during pregnancy, living in a warning signs state was associated with beliefs that use was not safe (β = 0.34 [95% CI, 0.17 to 0.51]), that people should be punished for use (β = 0.35 [95% CI, 0.24 to 0.47]), and that use was stigmatized (β = 0.35 [95% CI, 0.07 to 0.63]). Warning signs policies were not associated with use (adjusted odds ratio, 1.11 [95% CI, 0.22 to 5.67]). Conclusions and Relevance In this cross-sectional study of warning signs and cannabis-related use and beliefs, warning signs policies were not associated with reduced cannabis use during pregnancy or with people who used cannabis believing use during pregnancy was less safe but were associated with greater support for punishment and stigma among people who did not use cannabis.